NM_001348946.2:c.2685+3559C>T

Variant names:

• chr7-87527735-G-A
• rs7787082
• NM_001348946.2:c.2685+3559C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.2685+3559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,072 control chromosomes in the GnomAD database, including 8,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8745 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 33 publications found

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2685+3559C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2895+3559C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2685+3559C>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2685+3559C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2685+3559C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000488737.6	TSL:1	n.327+3559C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43914 AN: 151954 Hom.: 8714 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 44000 AN: 152072 Hom.: 8745 Cov.: 32 AF XY: 0.287 AC XY: 21297 AN XY: 74328

African (AFR) AF: 0.555 AC: 23020 AN: 41462

American (AMR) AF: 0.240 AC: 3660 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2249 AN: 5170

South Asian (SAS) AF: 0.220 AC: 1062 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1183 AN: 10582

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11198 AN: 67998

Other (OTH) AF: 0.268 AC: 565 AN: 2112

Alfa AF: 0.218 Hom.: 8998

Bravo AF: 0.313

Asia WGS AF: 0.339 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7787082; hg19: chr7-87157051;